Children learn through play, and they learn more than adults might expect. Science experiments are a great way to spark their curiosity, get their minds active, and encourage them to do something that doesn’t involve a screen. 54045-76-0, C4H2BrNO2S. A document type is Article, introducing its new discovery., Formula: C4H2BrNO2S
17beta-Hydroxysteroid dehydrogenase type 2 (17beta-HSD2) is responsible for the oxidation of the highly active estradiol (E2) and testosterone (T) into the less potent estrone (E1) and Delta4-androstene-3,17-dione (Delta4-AD), respectively. As 17beta-HSD2 is present in bones and as estradiol and testosterone are able to induce bone formation and repress bone resorption, inhibition of this enzyme could be a new promising approach for the treatment of osteoporosis. Herein, we describe the design, the synthesis and the biological evaluation of 24 new 17beta-HSD2 inhibitors in the 5-substituted thiophene-2-carboxamide class. Structure-activity and structure-selectivity relationships have been explored by variation of the sulfur atom position in the central core, exchange of the thiophene by a thiazole, substitution of the amide group with a larger moiety, exchange of the N-methylamide group with bioisosteres like N-methylsulfonamide, N-methylthioamide and ketone, and substitutions at positions 2 and 3 of the thiophene core with alkyl and phenyl groups leading to 2,3,5-trisubstituted thiophene derivatives. The compounds were evaluated on human and mouse enzymes. From this study, a novel highly potent and selective compound in both human and mouse 17beta-HSD2 enzymes was identified, compound 21 (IC 50(h17beta-HSD2) = 235 nM, selectivity factor toward h17beta-HSD1 = 95, IC50 (m17beta-HSD2) = 54 nM). This new compound 21 could be used for an in vivo proof of principle to demonstrate the true therapeutic efficacy of 17beta-HSD2 inhibitors in osteoporosis. New structural insights into the active sites of the human and mouse enzymes were gained.
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Reference：
Thiazole | C3H2827NS – PubChem,
Thiazole | chemical compound | Britannica